Tags

nmCRPC COE

  • [Availability of Local Therapy to Castration-Resistant Prostate Cancer for M0 Patients with Initial Prostate Specific Antigen 100 ng/ml or Higher].

    Prostate cancer patients with initial PSA 100 ng/ml or greater who received transrectal ultrasoundguided prostate biopsy and were staged as M0 by imaging studies from 2011 to 2014 in seven hospitals, were enrolled in the study.

    Published February 2, 2018
  • A Multinational, Randomised, Double-blind, Placebo-controlled, Phase III Efficacy and Safety Study of BAY1841788 (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer

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    A Multinational, Randomised, Double-blind, Placebo-controlled, Phase III Efficacy and Safety Study of BAY1841788 (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer


    Condition: Prostate Cancer Non-Metastatic, Castration-Resistant

    Intervention:

    • Drug: BAY1841788 (ODM-201)
    • Drug: Placebo

    Purpose: The purpose of this study is to assess the safety and efficacy of BAY1841788 (ODM-201) in patients with non-metastatic castration-resistant prostate cancer.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02200614

    Sponsor: Bayer

    Primary Outcome Measures:

    • Measure: Metastasis-Free Survival
    • Time Frame: Up to 72 months
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall Survival
    • Time Frame: Up to 72 months
    • Safety Issue:
    • Measure: Time to first symptomatic skeletal event (SSE)
    • Time Frame: Up to 72 months
    • Safety Issue:
    • Measure: Time to initiation of first cytotoxic chemotherapy for prostate cancer
    • Time Frame: Up to 72 months
    • Safety Issue:
    • Measure: Time to pain progression
    • Time Frame: Up to 72 months
    • Safety Issue:
    • Measure: Safety and tolerability of ODM-201
    • Time Frame: Up to 72 months
    • Safety Issue:

    Estimated Enrollment: 1500

    Study Start Date: September 12, 2014

    Phase: Phase 3

    Eligibility:

    • Age: minimum 18 Years maximum N/A
    • Gender: Male

    Inclusion Criteria:

    • Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
    • Castration-resistant prostate cancer (CRPC) with castrate level of serum testosterone.
    • Prostate-specific antigen doubling time of ≤ 10 months and PSA > 2ng/ml.
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
    • Blood counts at screening: haemoglobin ≥ 9.0 g/dl,absolute neutrophil count ≥ 1500/µl, platelet count ≥ 100,000/µl.
    • Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN, creatinine ≤ 2.0 x ULN.
    • Sexually active patients, unless surgically sterile, must agree to use condoms as an effective barrier method and refrain from sperm donation during the study treatment and for 3 months after the end of the study treatment.

    Exclusion Criteria:

    • History of metastatic disease at any time or presence of detectable metastases.
    • Acute toxicities of prior treatments and procedures not resolved to grade ≤ 1 or baseline before randomisation.
    • Prior treatment with: second generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor.
    • Use of estrogens or 5-α reductase inhibitors or AR inhibitors.
    • Prior chemotherapy or immunotherapy for prostate cancer.
    • Use of systemic corticosteroid.
    • Radiation therapy within 12 weeks before randomisation.
    • Severe or uncontrolled concurrent disease, infection or co-morbidity.
    • Treatment with bisphosphonate or denosumab within 12 weeks before randomisation.
    • Known hypersensitivity to the study treatment or any of its ingredients.
    • Major surgery within 28 days before randomisation.
    • Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
    • Uncontrolled hypertension.
    • Prior malignancy.
    • Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.
    • Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.
    • Treatment with any investigational drug within 28 days before randomisation.
    • Any condition that in the opinion of the investigator would impair the patients' ability to comply with the study procedures.

    Contact:

    • Bayer Clinical Trials Contact
    • +49 30 300139003

    Locations:

    • Homewood Alabama 35209 United States
      Anchorage Alaska 99503 United States
      Tucson Arizona 85704 United States
      Fountain Valley California 92708 United States
      La Jolla California 92093 United States
      Laguna Hills California 92653 United States
      Los Angeles California 90048 United States
      Los Angeles California 90073-1003 United States
      Orange California 92868 United States
      San Diego California 92120 United States
      Whittier California 90603 United States
      Denver Colorado 80211 United States
      Denver Colorado 80220 United States
      Parker Colorado 80134 United States
      Boca Raton Florida 33486 United States
      Miami Gardens Florida 33169 United States
      Orlando Florida 32803 United States
      Port Saint Lucie Florida 34952 United States
      Coeur d'Alene Idaho 83814 United States
      Chicago Illinois 60612 United States
      Evanston Illinois 60201-1613 United States
      Springfield Illinois 62704 United States
      Greenwood Indiana 46143 United States
      Indianapolis Indiana 46202 United States
      Jeffersonville Indiana 47130 United States
      West Des Moines Iowa 50266 United States
      Wichita Kansas 67226 United States
      New Orleans Louisiana 70121 United States
      Annapolis Maryland 21401 United States
      Baltimore Maryland 21201 United States
      Baltimore Maryland 21204 United States
      Salisbury Maryland 21801 United States
      Boston Massachusetts 02114 United States
      Farmington Hills Michigan 48334 United States
      Grand Rapids Michigan 49546 United States
      Royal Oak Michigan 48073 United States
      Woodbury Minnesota 55125 United States
      Omaha Nebraska 68114 United States
      Omaha Nebraska 68130 United States
      Lebanon New Hampshire 03756-0001 United States
      Edison New Jersey 08837 United States
      Englewood New Jersey 07631 United States
      Lawrenceville New Jersey 08648 United States
      Voorhees New Jersey 08043 United States
      Bronx New York 10461 United States
      Bronx New York 10469 United States
      Brooklyn New York 11215 United States
      New York New York 10016 United States
      Syracuse New York 13210 United States
      Asheboro North Carolina 27203 United States
      Durham North Carolina 27705 United States
      Gastonia North Carolina 28054 United States
      Canton Ohio 44718 United States
      Cincinnati Ohio 45212-1979 United States
      Cleveland Ohio 44195 United States
      Gahanna Ohio 43230 United States
      Middleburg Heights Ohio 44130 United States
      Oklahoma City Oklahoma 73104 United States
      Bala-Cynwyd Pennsylvania 19004 United States
      Bryn Mawr Pennsylvania 19010 United States
      Warwick Rhode Island 02886 United States
      Charleston South Carolina 29407 United States
      Myrtle Beach South Carolina 29572 United States
      Nashville Tennessee 37209 United States
      Dallas Texas 75231 United States
      Houston Texas 77027 United States
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      San Antonio Texas 78240 United States
      Falls Church Virginia 22031 United States
      Richmond Virginia 23235 United States
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      Wheeling West Virginia 26003 United States
      Buenos Aires Ciudad Auton. De Buenos Aires C1120AAT Argentina
      Rosario Santa Fe S2000KZE Argentina
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      Córdoba 5000 Argentina
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      Randwick New South Wales 2031 Australia
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      Douglas Queensland 4814 Australia
      South Brisbane Queensland 4101 Australia
      Fitzroy Victoria 3065 Australia
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      Kurralta Park 5037 Australia

      Linz Oberösterreich 4020 Austria

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      Calgary Alberta T2V 1P9 Canada

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      Halifax Nova Scotia B3H 2Y9 Canada

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      Hradec Kralove 500 05 Czechia

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      Emmendingen Baden-Württemberg 79312 Germany

      Heidelberg Baden-Württemberg 69115 Germany

      Kirchheim unter Teck Baden-Württemberg 73230 Germany

      Mühlacker Baden-Württemberg 75417 Germany

      Reutlingen Baden-Württemberg 72764 Germany

      Tübingen Baden-Württemberg 72076 Germany

      Waldshut-Tiengen Baden-Württemberg 79761 Germany

      Nürnberg Bayern 90489 Germany

      Planegg Bayern 82152 Germany

      Frankfurt Hessen 60590 Germany

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      Rostock Mecklenburg-Vorpommern 18107 Germany

      Hannover Niedersachsen 30625 Germany

      Herzberg Am Harz Niedersachsen 37412 Germany

      Holzminden Niedersachsen 37603 Germany

      Osnabrück Niedersachsen 49076 Germany

      Düsseldorf Nordrhein-Westfalen 40225 Germany

      Köln Nordrhein-Westfalen 50931 Germany

      Mülheim Nordrhein-Westfalen 45468 Germany

      Münster Nordrhein-Westfalen 48149 Germany

      Wuppertal Nordrhein-Westfalen 42103 Germany

      Mainz Rheinland-Pfalz 55131 Germany

      Homburg Saarland 66421 Germany

      Magdeburg Sachsen-Anhalt 39112 Germany

      Dresden Sachsen 01307 Germany

      Markkleeberg Sachsen 04416 Germany

      Berlin 10115 Germany

      Berlin 12200 Germany

      Hamburg 20246 Germany

      Hamburg 22081 Germany

      Tübingen 72076 Germany

      Abelokipi - Athens 115 26 Greece

      Athens 115 27 Greece

      Athens 11522 Greece

      Athens 11527 Greece

      Athens 11528 Greece

      Glyfada/Athens 16675 Greece

      Ioannina 45500 Greece

      Thessaloniki-Moudanion 57001 Greece

      Budapest 1085 Hungary

      Budapest 1145 Hungary

      Budapest 1204 Hungary

      Debrecen 4032 Hungary

      Gyor 9024 Hungary

      Nyiregyhaza 4400 Hungary

      Szeged 6725 Hungary

      Szekszard 7100 Hungary

      Szolnok 5004 Hungary

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      Beer Sheva 8410101 Israel

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      Haifa 35152 Israel

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      Ramat Gan 5262000 Israel

      Tel Aviv 6423906 Israel

      Zefat 1311001 Israel

      Chieti Abruzzo 66100 Italy

      Catanzaro Calabria 88100 Italy

      Napoli Campania 80131 Italy

      Napoli Campania Italy

      Bologna Emilia-Romagna 40138 Italy

      Forlì-Cesena Emilia-Romagna 47014 Italy

      Modena Emilia-Romagna 41124 Italy

      Parma Emilia-Romagna 43126 Italy

      Roma Lazio 00144 Italy

      Roma Lazio 00189 Italy

      Como Lombardia Italy

      Milano Lombardia 20159 Italy

      Novara Piemonte 28100 Italy

      Torino Piemonte 10043 Italy

      Torino Piemonte 10060 Italy

      Lecce Puglia 73100 Italy

      Catania Sicilia 95123 Italy

      Messina Sicilia 98125 Italy

      Palermo Sicilia 90127 Italy

      Arezzo Toscana 52100 Italy

      Siena Toscana 53100 Italy

      Nagoya Aichi 466-8560 Japan

      Nagoya Aichi 466-8650 Japan

      Kashiwa Chiba 277-8577 Japan

      Iizuka Fukuoka 820-8505 Japan

      Kurume Fukuoka 839-0863 Japan

      Koriyama Fukushima 963-8052 Japan

      Maebashi Gunma 371-8511 Japan

      Otake Hiroshima 739-0696 Japan

      Sapporo Hokkaido 060-8543 Japan

      Kobe Hyogo 650-0047 Japan

      Higashiibaraki Ibaraki 311-3193 Japan

      Kahoku-gun Ishikawa 920-0293 Japan

      Kanazawa Ishikawa 920-8530 Japan

      Sagamihara Kanagawa 252-0375 Japan

      Yokohama Kanagawa 232-0024 Japan

      Yokosuka Kanagawa 238-8558 Japan

      Sendai Miyagi 980-8574 Japan

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      Ueda Nagano 386-8610 Japan

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      Yufu Oita 879-5593 Japan

      Kurashiki Okayama 710-8602 Japan

      Higashiosaka Osaka 578-8588 Japan

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      Takatsuki Osaka 569-1192 Japan

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      Hamamatsu Shizuoka 431-3192 Japan

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      Bunkyo-ku Tokyo 113-8431 Japan
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      Chiba 260-8717 Japan

      Fukui 910-8526 Japan

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      Kyoto 602-8566 Japan

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      Okayama 700-8558 Japan

      Osaka 541-8567 Japan

      Osaka 545-8586 Japan

      Osaka 558-8558 Japan

      Toyama 930-0194 Japan

      Donggu, Gwangju Gwang''yeogsi 501-757 Korea, Republic of

      Seoul Seoul Teugbyeolsi 135-720 Korea, Republic of

      Chungchungbuk-do 361-711 Korea, Republic of

      Daegu 700-701 Korea, Republic of

      Daegu 700-712 Korea, Republic of

      Incheon 405-760 Korea, Republic of

      Seoul 110-744 Korea, Republic of

      Seoul 120-752 Korea, Republic of

      Seoul 135-710 Korea, Republic of

      Seoul 137-701 Korea, Republic of

      Seoul 138-736 Korea, Republic of

      Daugavpils LV5401 Latvia

      Jelgava LV-3001 Latvia

      Leipaja LV-3401 Latvia

      Riga LV-1001 Latvia

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      Riga LV-1038 Latvia

      Kaunas LT-50009 Lithuania

      Klaipeda LT-92288 Lithuania

      Vilnius LT-08660 Lithuania

      Vilnius LT-08661 Lithuania

      La Victoria Arequipa Peru

      Lima 27 Peru

      Lima LIMA 11 Peru

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      Elblag 82-300 Poland

      Gdansk 80-952 Poland

      Lodz 90-302 Poland

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      Otwock Poland

      Rzeszow 35-922 Poland

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      Wroclaw 50-556 Poland

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      Santa Maria da Feira Porto 4520-211 Portugal

      Almada 2801-951 Portugal

      Braga 4710-243 Portugal

      Coimbra 3000-075 Portugal

      Guimaraes 4835-044 Portugal

      Lisboa 1093-023 Portugal

      Lisboa 1150-199 Portugal

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      Matosinhos 4464-513 Portugal

      Porto 4200-072 Portugal

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      Bucuresti 22328 Romania

      Bucuresti 41345 Romania

      Bucuresti 50659 Romania

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      Cluj-Napoca 400015 Romania

      Cluj-Napoca 400132 Romania

      Craiova 200385 Romania

      Craiova 200642 Romania

      Oradea 410159 Romania

      Ploiesti 100337 Romania

      Targu-Mures 540103 Romania

      Arkhangelsk 163045 Russian Federation

      Barnaul 656049 Russian Federation

      Chelyabinsk 454087 Russian Federation

      Ivanovo 153040 Russian Federation

      Kazan 420029 Russian Federation

      Krasnoyarsk 660022 Russian Federation

      Moscow 105425 Russian Federation

      Moscow 117997 Russian Federation

      Moscow 125284 Russian Federation

      Moscow 129301 Russian Federation

      Nizhny Novgorod 603001 Russian Federation

      Novosibirsk 630099 Russian Federation

      Obninsk 249036 Russian Federation

      Omsk 644013 Russian Federation

      Orenburg 460021 Russian Federation

      Pyatigorsk 357502 Russian Federation

      Rostov-on-Don 344022 Russian Federation

      Saratov 410012 Russian Federation

      St. Petersburg 191104 Russian Federation

      St. Petersburg 194017 Russian Federation

      St. Petersburg 194354 Russian Federation

      St. Petersburg 197022 Russian Federation

      St. Petersburg 197758 Russian Federation

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      Tyumen 625041 Russian Federation

      Ufa 450008 Russian Federation

      Volgograd 400138 Russian Federation

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      Martin 036 59 Slovakia

      Presov 080 81 Slovakia

      Skalica 90982 Slovakia

      Trencin 91101 Slovakia

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      George Eastern Cape 6530 South Africa

      Port Elizabeth Eastern Cape 6045 South Africa

      Johannesburg Gauteng 2193 South Africa

      Pretoria Gauteng 0083 South Africa

      Durban Kwazulu-Natal 4126 South Africa

      Paarl Western Cape 7646 South Africa

      Rondebosch Western Cape 7700 South Africa

      Somerset West Western Cape 7130 South Africa

      Cape Town 7505 South Africa

      Cape Town 7925 South Africa

      Elche Alicante 03203 Spain

      Cádiz Andalucía 11009 Spain

      L'Hospitalet de Llobregat Barcelona 08907 Spain

      Sabadell Barcelona 08208 Spain

      Terrassa Barcelona 08221 Spain
      Jerez de la Frontera Cádiz 11407 Spain
      Manacor Illes Baleares 07500 Spain
      Palma de Mallorca Illes Baleares 07010 Spain
      Alcorcón Madrid 28922 Spain
      Fuenlabrada Madrid 28942 Spain
      Barakaldo Vizcaya 48903 Spain

      Barcelona 08025 Spain

      Barcelona 08035 Spain

      Barcelona 08036 Spain

      Bilbao 48013 Spain

      Córdoba 14004 Spain

      Granada 18012 Spain

      Granada 18014 Spain

      Lugo 27003 Spain

      Madrid 28007 Spain

      Madrid 28040 Spain

      Madrid 28041 Spain

      Madrid 28046 Spain

      Madrid 28050 Spain

      Málaga 29010 Spain

      Pamplona 31008 Spain

      Salamanca 37007 Spain

      Sevilla 41013 Spain

      Sevilla 41071 Spain

      Valencia 46009 Spain

      Valencia 46015 Spain

      Valencia 46026 Spain

      Valencia 46026 Spain

      Borås 501 82 Sweden

      Göteborg 413 45 Sweden

      Stockholm 171 76 Sweden

      Uppsala 751 85 Sweden

      Örebro 701 85 Sweden

      Kaohsiung City , Taiwan

      Kaoshiung 813 Taiwan

      Taichung 40705 Taiwan

      Taipei 10002 Taiwan

      Taoyuan 333 Taiwan

      Ankara 06560 Turkey

      Ankara 6100 Turkey

      Istanbul 34730 Turkey

      Izmir Turkey

      Manisa 45010 Turkey

      Sivas 58140 Turkey

      Chernivtsi 58002 Ukraine

      Dnipropetrovsk 49102 Ukraine

      Kharkiv 61037 Ukraine

      Kryvyi Rih 50048 Ukraine

      Kyiv 252053 Ukraine

      Kyiv 2660 Ukraine

      Uzhgorod 88014 Ukraine

      Zaporozhye 69600 Ukraine

      Reading Berkshire RG1 5AN United Kingdom

      Llanelli Carmarthenshire SA14 8QF United Kingdom

      Romford Essex RM7 0AG United Kingdom

      Stevenage Hertfordshire SG1 4AB United Kingdom

      Maidstone Kent ME16 9QQ United Kingdom

      Preston Lancashire PR2 4HT United Kingdom

      Bebington Merseyside CH63 4JY United Kingdom

      Scunthorpe North East Lincolnshire DN15 7BH United Kingdom

      Bath Somerset BA1 3NG United Kingdom

      Stoke-on-Trent Staffordshire ST4 6QG United Kingdom

      Dudley West Midlands DY1 2HQ United Kingdom

      Huddersfield West Yorkshire HD3 3EA United Kingdom

      Wakefield West Yorkshire WF1 4DG United Kingdom
      Worcester Worcestershire WR5 1DD United Kingdom
      Cardiff CF14 4XN United Kingdom>
      Dundee DD2 1UB United Kingdom
      Glasgow G12 0YN United Kingdom
      Kent DA2 8DA United Kingdom
      London SW17 0QT United Kingdom
      London SW3 6JJ United Kingdom
      Wrexham LL13 7TD United Kingdom

    View trial on ClinicalTrials.gov


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    Published March 7, 2017
  • An Unmet Need is Met: (The PROSPER Study): Evaluating the Safety and Efficacy Study of Enzalutamide in Patients with Nonmetastatic Castration- Resistant Prostate Cancer

    Published in Everyday Urology - Oncology Insights: Volume 3, Issue 1
    For men with non-metastatic, castration-resistant prostate cancer (nmCRPC), who are invariably at risk of metastasis, the PROSPER trial clearly demonstrated that combining enzalutamide to androgen-deprivation therapy (ADT) resulted in prolonging metastasis-free survival by a median of 22 months compared with ADT plus placebo in a global, double-blind, phase III study (Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer), presented at the plenary session of ASCO GU 2018.1
    Published August 14, 2018
  • Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide.

    : Mutations in the androgen receptor (AR) ligand-binding domain (LBD), such as F877L and T878A, have been associated with resistance to next-generation AR-directed therapies. ARN-509-001 was a phase I/II study that evaluated apalutamide activity in castration-resistant prostate cancer (CRPC).

    Published June 25, 2017
  • Apalutamide Delayed CRPC Metastasis by More Than 2 Years - SPARTAN

    Men with high-risk, non-metastatic, castration-resistant prostate cancer who received apalutamide, an investigational, next-generation non-steroidal androgen receptor inhibitor, survived without disease progression a median of 2 years longer than patients who received placebo in an interim analysis of the global phase III SPARTAN trial.1
    Published February 28, 2018
  • Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

    Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.
    Published February 9, 2018
  • ASCO GU 2018: First Presentation - PROSPER: Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)

    San Francisco, CA (UroToday.com) Dr. Maha Hussain provided the first presentation of the phase III randomized double-blind controlled trial, the following men were eligible for inclusion:
    Published February 9, 2018
  • ASCO GU 2019: ARAMIS: Efficacy and Safety of Darolutamide in Nonmetastatic Castration-Resistant Prostate Cancer

    San Francisco, CA (UroToday.com) The use of androgen-axis targeted agents, specifically enzalutamide and abiraterone, have drastically changed the landscape of advanced prostate cancer management. Just last year, at GU ASCO 2018, two landmark trials were presented – SPARTANand PROSPER - which were conducted in nonmetastatic CRPC (nmCRPC) patients.1,2 PROSPER specifically assesses enzalutamide in the M0 CRPC setting, while SPARTAN focused on apalutamide-ARN-509 (APA). Apalutamide is a next-generation competitive inhibitor of the androgen receptor under development for the treatment of patients with prostate cancer but perhaps with greater potency and reduced CNS effects. Both demonstrated ~2 year metastases-free survival benefit compared to ADT alone and there was early evidence of OS benefit.
    Published February 15, 2019
  • CUOS 2019: Treating M0 or Non-metastatic Castration-resistant Prostate Cancer

    Toronto, Ontario (UroToday.com) Dr. Neil Fleshner presented the question in debate of whether we should be treating non-metastatic castrate-resistant prostate cancer (nmCRPC) patients or wait until they have developed metastases.

    He began his discussion stating the enormous changes that have occurred in the last 15 years in the field of advanced prostate cancer. Many new treatments have been added that extend survival. These include chemotherapy (docetaxel, cabazitaxel), Sipuleucel T, androgen axis inhibitors (abiraterone, enzalutamide, apalutamide) and Radium 223. Additionally, supportive agents have been added including bone-targeted therapies (denosumab and zoledronic acid).
    Published January 11, 2019
  • Darolutamide’s FDA Rolling Submission Completed

    San Francisco, CA USA (UroToday.com) -- Orion and Bayer have announced the completion of the rolling submission of a New Drug Application (NDA) for Darolutamide to the US Food and Drug Administration (FDA).
    Published February 27, 2019
  • EAU 2019: Darolutamide Elicits a Strong PSA Response in Men with nmCRPC: Results from the ARAMIS Study

    Barcelona, Spain (UroToday.com) At EAU 2019, Dr. Teuvo Tammela presented results of the recently published ARAMIStrial. Non-metastatic (M0) CRPC (nmCRPC) is defined as a rising PSA in the setting of non-metastatic disease in the castrate state. The primary goal of treatment for these patients is the delay of metastases, considering that morbidity and mortality are both significantly worse following progression to metastases.
    Published March 18, 2019
  • FDA Approves Apalutamide, First Treatment for Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)

    Truckee, CA (UroToday.com) FDA has approved apalutamide, the first treatment for nonmetastatic castration-resistant prostate cancer, based on results from a phase 3 study that showed the drug reduced the risk of metastasis or death by 72% and improved median metastasis-free survival by more than 2 years.
    Published February 15, 2018
  • Impact of age, comorbidity, and PSA doubling time on long-term competing risks for mortality among men with non-metastatic castration-resistant prostate cancer

    Understanding competing risks for mortality is critical in determining prognosis among men with non-metastatic castration-resistant prostate cancer (nmCRPC), a disease state that often affects older men and has substantial heterogeneity in risk of cancer mortality.

    Published October 8, 2018
  • Japanese Research for Patients With Non-metastatic Castration Resistant Prostate Cancer - Enzalutamide

    {{header-clinical-trials-navigation}}

    Japanese Research for Patients With Non-metastatic Castration Resistant Prostate Cancer - Enzalutamide


    Condition: Prostate Cancer

    Intervention:

    • Drug: Enzalutamide

    Purpose: The purpose of this study is to investigate the efficacy and safety of enzalutamide in patients with non-metastatic castration resistant prostate cancer. The total duration of the study will be 5 years. All patients will receive enzalutamide 160 mg (four 40 mg capsules) orally once daily. The treatment will be started at Visit 0 within one week after enrollment. Visit 1 is at 2 weeks after the treatment started; clinical assessments are conducted on adverse events and the Japanese version of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scales. Patients who are considered to be adequate by the investigator can continue the treatment with 12-week cycle visit (counted from initial dose) until patients meet withdrawal criteria. Patients will be followed up at 2 and 3 years after enrollment and at 3 years after the last participant enrollment. The end of the study is defined as follow-up assessment date at 3 years after the last participant enrollment. Patients will primarily be assessed by prostate-specific antigen (PSA) progression-free survival (PFS).

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT02588001

    Sponsor: Translational Research Informatics Center, Kobe, Hyogo, Japan

    Primary Outcome Measures:

    • Measure: PSA-progression-free survival (PSA-PFS)
    • Time Frame: 6 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Overall survival (OS)
    • Time Frame: 6 years
    • Safety Issue:
    • Measure: Progression-free survival (PFS)
    • Time Frame: 6 years
    • Safety Issue:
    • Measure: Metastasis free survival (MFS)
    • Time Frame: 6 years
    • Safety Issue:
    • Measure: Time-to-PSA-progression (TTPP)
    • Time Frame: 6 years
    • Safety Issue:
    • Measure: PSA response rate
    • Time Frame: At week 2, and every 12 weeks for up to 6 years after initial dose
    • Safety Issue:
    • Measure: Time to first use of chemotherapy (TFC)
    • Time Frame: 6 years
    • Safety Issue:
    • Measure: QOL assessment using Japanese version of the FACT-P scales
    • Time Frame: Baseline, week 2, week 60, at withdrawal of treatment and at end of treatment for up to 6 years
    • Safety Issue:
    • Measure: Medication adherence (dosage)
    • Time Frame: 6 years
    • Safety Issue:
    • Measure: Medication adherence (duration)
    • Time Frame: 6 years
    • Safety Issue:
    • Measure: Medication adherence (ratio)
    • Time Frame: 6 years
    • Safety Issue:
    • Measure: Safety assessment on the incidence and severity of adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
    • Time Frame: 6 years
    • Safety Issue:

    Estimated Enrollment: 60

    Study Start Date: October 1, 2015

    Eligibility:

    • Age: minimum 20 Years maximum N/A
    • Gender: Male

    Inclusion Criteria:

    1. Patients with histologically or cytologically confirmed prostate cancer
    2. Patients with history of radical prostatectomy or radiation therapy for radical treatment
    3. Patients who receive continuous androgen deprivation therapy using both gonadotropin-releasing hormone (GnRH) agonist and antagonist, or using surgical castration
    4. Patients with serum testosterone 1.73 nmol/L (0.50 ng/dL) or less
    5. Patients with history of bicalutamide or flutamide at any time after first recurrence confirmed since radical treatment completed
    6. Patients with 3 increased PSA test results which measured consecutively at least one week apart during androgen deprivation therapy
    7. Patients with serum PSA 1 micrograms/L (1 ng/mL) or more
    8. Patients with no confirmed remote metastasis after diagnosis of prostate cancer (excluding lymph nodes metastasis with a minor axis of less than 15 mm which considered to be nonmeasurable in the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1)
    9. Patients with asymptomatic prostate cancer
    10. Patients with the Eastern Cooperative Oncology Group (ECOG) performance status 0-1
    11. Patients with life expectancy of at least 12 months
    12. Patients who have signed written informed consent to participate in this study

    Exclusion Criteria:

    1. Patients with history of any chemotherapy (including estramustine phosphate sodium hydrate (JAN)) or treatment with enzalutamide or abiraterone acetate
    2. Patients with history of steroid usage as treatment for prostate cancer
    3. Patients with history of 5-alpha-reductase inhibitor, estrogen or steroidal antiandrogen within past 4 weeks prior to initial administration of enzalutamide
    4. Patients with history of malignant tumor other than prostate cancer within past 3 years
    5. Patients with history of seizure or predisposing disease of seizure
    6. Patients with severe liver dysfunction
    7. Patients with a previous history of hypersensitivity to any component of drugs which will be administered in this study
    8. Patients who considered to be inappropriate for the study participation by the investigator.

    Contact:

    • Mikio Sugimoto, MD, Ph.D.
    • +81-87-898-5111

    Locations:

    • Kagawa University Faculty of Medicine
    • Kita-gun Kagawa-prefecture 761-0793 Japan
    • University of Miyazaki Faculty of Medicine
    • Miyazaki-city Miyazaki-prefecture 889-1692 Japan
    • Tokyo Medical Center
    • Meguro-ku Tokyo 152-8902 Japan
    • The Jikei university school of medicin
    • Minato-ku Tokyo 105-8461 Japan

    View trial on ClinicalTrials.gov


    {{footer-clinical-trials-navigation}}
    Published June 29, 2017
  • MDACC 2018: An Update on the Treatment of M0 CRPC

    Houston, TX (UroToday.com) Within the past year the landscape of M0 CRPC has changed dramatically on the heels of 2 studies using early administration of 2nd generation androgen receptor blockers. Both apalutamide and enzalutamide have multiple inhibitor mechanisms for the AR receptor and have been accepted in the metastatic setting.
    Published November 10, 2018
  • Non metastatic CRPC: The Five Essentials - Charles Ryan

    The ASCO Genitourinary Cancers Symposium for 2018 will feature the presentation of two-phase III studies of AR directed therapy in patients with non-metastatic CRPC. Before we get these results we can reflect on why these two studies were done in this patient population in the first place, and what exact clinical need is being addressed by the development of the studies in this space. 
    Published February 1, 2018
  • The Multidisciplinary Approach to Prostate Cancer Management: From Diagnosis and Beyond

    Published in Everyday Urology - Oncology Insights: Volume 2, Issue 2
    Everyday Urology-Oncology Insights: Volume 2, Issue 2

    When patients receive a diagnosis of cancer it can be devastating. Suddenly their world is turned upside down, populated by doctors, diagnostic tests, and treatments.

    The standard process for newly diagnosed patients with prostate cancer is a chronologically linear and often one-dimensional process managed by urologists.3 If the patient’s diagnosis is based on biopsy results, the urologist discusses treatment options with the patient and his family. This may be followed by referral to another specialist such as a medical and/or radiation oncologist depending on their risk stratification.4
    Published September 5, 2017
  • Treatment Advances in Non Metastatic Castration-Resistant Prostate Cancer

    Since Drs. Huggins and Hodges demonstrated the androgen dependent nature of prostate cancer in the 1940’s, androgen deprivation therapy (ADT) has been the mainstay treatment (albeit not curative) of advanced disease.1 ADT induces a PSA decline, which may be a viable treatment for a period of time, however a patient will eventually develop a castration-resistant state by which the serum PSA level increases despite a castrate level of testosterone. The transformation to castration-resistant prostate cancer (CRPC) typically occurs before conventional imaging visualization of metastatic disease, the landmark time-point between non-metastatic (nmCRPC) and metastatic CRPC (mCRPC). 

    The PCWG3 consensus for PSA progression on ADT is the most accepted definition of nmCRPC: a 25% PSA increase from nadir (starting PSA ≥1.0 ng/mL), with a minimum rise of 2 ng/mL in the setting of castrate testosterone (< 50 ng/dL).2 The most common clinical scenario of nmCRPC is no detectable disease in the primary site, no detected lymph nodes by CT or MRI, and no disease in the bone or visceral organs.3 The most commonly used imaging for conventional detection of metastasis is a technetium-99 bone scintigraphy scan to detect bone metastases, and a CT (or MRI if CT contraindicated) of the chest, abdomen and pelvis for evaluating soft tissue metastases. Prior to the trials and data presented in this article, one in three men with nmCRPC would develop metastatic disease within 2 years.4 The objective of this article is to review the practice changing data presented in 2018 for patients with nmCRPC and discuss studies and opinions that have emerged since phase III randomized controlled trial (RCT) data was published. 


    Non Metastatic CRPC: Recent Clinical Trials

    Enzalutamide is a novel androgen receptor (AR) signaling competitive inhibitor of androgen binding. It inhibits nuclear translocation of the AR, DNA binding, and coactivator recruitment. Two large phase III trials confirmed enzalutamide efficacy and ability to improve overall survival (OS) versus placebo in men with mCRPC both in the pre-chemotherapy (PREVAIL study5,6) and post-chemotherapy (AFFIRM study7) disease state. These results set the stage for assessing efficacy of enzalutamide in early disease states. Given that enzalutamide binds the AR with a 5-8-fold greater affinity than bicalutamide, the STRIVE trial (published in 2016) was a mixed population of men diagnosed with non-metastatic (n=139) or metastatic (n=257) CRPC randomized 1:1 to receive enzalutamide (160 mg/day) or bicalutamide (50 mg/day), with both arms remaining on ADT.8 Enzalutamide reduced the risk of progression or death by 76% compared with bicalutamide (HR 0.24, 95%CI 0.18-0.32), as well as demonstrated significant improvements in all key secondary end points: time to PSA progression (HR 0.19, 95%CI 0.14-0.26), proportion of patients with a ≥ 50% PSA response (81% v 31%; P < .001), and radiographic progression free survival (PFS) in metastatic patients (HR 0.32, 95%CI 0.21-0.50). Importantly, these beneficial effects with enzalutamide were observed in both the nonmetastatic and metastatic subgroups. Even before results of the STRIVE trial were published, recruitment was already underway for two large phase III trials that would report in 2018 and change clinical practice for men with nmCRPC: the PROSPER and SPARTAN trials. 

    The PROSPER trial was an international, double-blind, randomized, placebo-controlled, phase 3 trial approved at more than 300 sites in 32 countries.9 In this trial, 1,401 patients with nmCRPC were randomized 2:1 to enzalutamide vs placebo, with a primary outcome of metastasis-free survival (MFS). Secondary endpoints were time to PSA progression, time to first use of new therapy, and OS. The median MFS was 36.6 months in the enzalutamide arm versus 14.7 months in the placebo group: a 71% improvement for men receiving enzalutamide (HR 0.29, 95%CI 0.24-0.35). Time to PSA progression was 37.2 months for the enzalutamide group vs 3.9 months for the placebo arm (HR 0.07, 95%CI 0.05-0.08), and time to subsequent therapy was 39.6 months for enzalutamide patients compared to 17.7 for the placebo group (HR 0.21, 95%CI 0.17-0.26). At the interim analysis for OS, the HR was 0.80 (favoring enzalutamide), but was not statistically significant (p=0.15).

    Apalutamide is a nonsteroidal anti-androgen AR inhibitor, which binds to the ligand-binding domain of the AR after nuclear translocation; apalutamide has a 7-10-fold higher affinity for the AR than bicalutamide. The SPARTAN trial was a multi-institutional, double-blind, randomized, placebo-controlled, phase 3 trial at 332 sites in 26 countries in North America, Europe, and Asia-Pacific region.10 This trial randomized 1,207 men 2:1 to receive apalutamide vs placebo. In the planned primary analysis at 378 events, median MFS was 40.5 months in the apalutamide group compared with 16.2 months in the placebo group (HR for metastasis or death 0.28, 95% CI 0.23-0.35). Time to symptomatic progression was significantly longer with apalutamide than with placebo (HR 0.45, 95%CI 0.32-0.63). The conclusions from SPARTAN were that apalutamide decreased the risk of metastasis or death by 72% and prolonged the median MFS by more than two years in men with high-risk nmCRPC. Furthermore, the MFS benefit was consistent across all subgroups, and the results were supported by consistent improvement across all evaluable endpoints: time to metastasis, PFS, time to symptomatic progression, time to PSA progression, and PSA decline.


    Non Metastatic CRPC Since PROSPER and SPARTAN

    Following presentation of the SPARTAN trial at the GU ASCO annual meeting in February 2018 and concomitant publication in The New England Journal of Medicine (NEJM)10, the FDA moved quickly on February 14, 2018 to approve apalutamide (240 mg daily) for men with nmCRPC. The PROSPER trail was also published in NEJMin June 20189, and enzalutamide (160 mg daily) also gained FDA approval on July 13, 2018. 

    Prior to FDA approval of enzalutamide, the American Urological Association (AUA) provided an amendment to their AUA CRPC Guideline11, first presented at the AUA 2018 annual meeting. This amendment focused solely on Index Patient 1—patients with non-metastatic CRPC, providing four updated Guideline Statements11:
    • Guideline Statement 1:Clinicians should offer apalutamide or enzalutamide with continued androgen deprivation to patients with non-metastatic CRPC at high risk for developing metastatic disease (Standard; Evidence Level Grade A [apalutamide]/Grade B [enzalutamide])
    • Guideline Statement 2:Clinicians may recommend observation with continued androgen deprivation to patients with non-metastatic CRPC at high risk for developing metastatic disease who do not want or cannot have one of the standard therapies (Recommendation; Evidence Level Grade C)
    • Guideline Statement 3:Clinicians may offer treatment with a second-generation androgen synthesis inhibitor (i.e. abiraterone + prednisone) to select patients with non-metastatic CRPC at high risk for developing metastatic disease who do not want or cannot have one of the standard therapies and are willing to accept observation (Option; Evidence Level Grade C)
    • Guideline Statement 4:Clinicians should not offer systemic chemotherapy or immunotherapy to patients with non-metastatic CRPC outside the context of a clinical trial (Recommendation; Evidence Level Grade C)
    Based on data from PROSPER and SPARTAN, clinicians are now equipped with two FDA approved agents for prescribing to patients with nmCPRC. However, in the absence of a head-to-head trial (which is unlikely), the comparative efficacy and toxicity of these two agents was the basis for an indirect treatment comparison of apalutamide and enzalutamide recently published in European Urologic Oncology. For this study, Wallis et al. 12 pooled data from PROSPER and SPARTAN resulting in 2,608 patients of whom 806 received apalutamide, 933 received enzalutamide, and 869 received placebo, in addition to ongoing ADT. Study methodology and inclusion criteria were similar between studies though PROSPER required a serum PSA level ≥2ng/mL while no such requirement was present in the SPARTAN trial. Despite this difference in study inclusion criteria, the patients in the two study cohorts had similarly aggressive disease characteristics with median PSADT in both studies between 3 and 5 months.

    As noted above, both apalutamide (HR 0.28, 95% CI 0.23-0.35) and enzalutamide (HR 0.29, 95% CI 0.24-0.35) demonstrated statistically significant improvements in MFS compared with placebo. On indirect comparison of apalutamide and enzalutamide, there was no significant difference in MFS between the two agents (HR 1.04, 95% CI 0.78-1.37). Similarly, there were no significant differences in time to PSA progression, OS, any AEs, serious AEs, or AEs leading to treatment discontinuation. The authors concluded that while indirect comparisons cannot supplant direct comparative data, the analysis suggests that apalutamide and enzalutamide are similarly effective in delaying metastases for patients with nmCRPC.

    Since indirect comparison between enzalutamide and apalutamide demonstrated no appreciable difference in efficacy or toxicity, subsequent studies and editorials have focused on  several initiatives, including quality of life. In a letter to the NEJM editor, Rachner and colleagues noted that patients receiving apalutamide had a higher rate of bone fracture (11.7%) compared to placebo (6.5%)13, noting that only 10% of patients in SPARTAN received bone-protective therapy at the beginning of the trial. In the author’s response to this editorial, Smith et al. noted that patients treated with enzalutamide in the PROSPER trial had a higher rate of falls and fractures than the placebo patients, attributing these findings to a medication case effect. 14 This dialogue highlights the NCCN guideline recommendations to assess for fracture risk and treat with a bisphosphonate or denosumab when the absolute fracture risk warrants drug therapy.

    Specific health-related quality of life (HRQOL) data from both trials has also been presented since original publication of the phase III trials. The SPARTAN trial collected Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaire data at baseline, day 1 of cycle 1 (before dose), day 1 of treatment cycles 1-6, day 1 of every two cycles from cycles 7 to 13, and day 1 of every four cycles thereafter.15 Notably, FACT-P and EQ-5D-3L scores were associated with a preservation of HRQOL from baseline to cycle 29 in the apalutamide group. At baseline, the mean for FACT-P total score in both the apalutamide and placebo groups were consistent with the FACT-P general population norm for American adult men. Furthermore, group mean patient-reported outcome scores over time showed that HRQOL was maintained from baseline after initiation of apalutamide and similar over time. Mean change from baseline analysis showed that HRQOL deterioration was more apparent in the placebo group than those receiving apalutamide. The SPARTAN investigators noted that in addition to improved MFS and time to symptomatic progression compared to men receiving placebo, they achieved these improved outcomes while preserving quality of life.

    Similarly, PROSPER has reported results of HRQOL and pain evaluations.16 FACT-P and Brief Pain Inventory, Short Form, were used to assess HRQOL and pain at baseline and every 16 weeks during treatment. The authors defined pain progression as ≥2 points in pain severity items and mean scores increase from baseline. Baseline characteristics and scores were similar between the enzalutamide and placebo arms with low pain (median 0) and high HRQoL (median FACT-P total score: 121). Decrease in attrition rate was greater in the placebo arm (53%) compared to the enzalutamide arm (68%), mainly due to disease progression at week 49. Most patients reported no change or improvement in HRQoL. The proportion of patients with pain progression at week 49 was similar between those receiving enzalutamide (11–20%) and placebo (14–21%). There was a non-statistically significant lower risk of pain progression observed with enzalutamide vs. placebo in the confirmed analysis (HR 0.78–0.93, p > 0.05). Furthermore, there was a statistically significant lower risk of deterioration observed for patients receiving enzalutamide for FACT-P total (HR 0.83, 95%CI 0.69-0.99), FACT Advanced Prostate Symptom Index (HR 0.79, 95%CI 0.65-0.94), prostate cancer subscale (HR 0.79, 95%CI 0.67-0.93), and emotional well-being (HR 0.69, 95%CI 0.55-0.86). Taking HRQOL data together from both PROSPER and SPARTAN, enzalutamide and apalutamide are both associated with maintaining quality of life throughout the trial follow-up.


    Conclusions

    2018 has been a landmark year for advancing treatment options for patients with nmCRPC, with two phase III RCTs reporting unprecedented hazard ratios for delaying metastasis for patients treated with enzalutamide and apalutamide. Since initial trial publication, HRQOL studies have confirmed maintenance of quality of life on these medications, although there may be concerns for increased risk of bone fracture combining these powerful AR targeted agents with ADT. Looking forward, the ongoing ARAMIS trial assessing darolutamide (another AR pathway inhibitor) in patients with nmCRPC (with similar inclusion criteria and outcomes as PROSPER and SPARTAN) may provide clinicians with another agent in the medical armamentarium for treatment of nmCRPC. This trial has an estimated completion date of September 2018.
    Written by: Zachary Klaassen, MD
    References: 1. Huggins C, Hodges CV. Studies on prostate cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1:293-7.
    2. Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34:1402-18.
    3. Mateo J, Fizazi K, Gillessen S, Heidenreich A, Perez-Lopez R, Oyen WJG, et al. Managing Nonmetastatic Castration-resistant Prostate Cancer. Eur Urol. 2018.
    4. Smith MR, Kabbinavar F, Saad F, Hussain A, Gittelman MC, Bilhartz DL, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23:2918-25.
    5. Beer TM, Armstrong AJ, Rathkopf D, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in Men with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study. Eur Urol. 2017;71:151-4.
    6. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424-33.
    7. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187-97.
    8.  Penson DF, Armstrong AJ, Concepcion R, Agarwal N, Olsson C, Karsh L, et al. Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. J Clin Oncol. 2016;34:2098-106.
    9. Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2018;378:2465-74.
    10. Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018;378:1408-18.
    11. Lowrance WT, Murad MH, Oh WK, Jarrard DF, Resnick MJ, Cookson MS. Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2018. J Urol. 2018.
    12. Wallis CJD, Chandrasekar T, Goldberg H, Klotz L, Fleshner N, Satkunasivam R, et al. Advanced Androgen Blockage in Nonmetastatic Castration-resistant Prostate Cancer: An Indirect Comparison of Apalutamide and Enzalutamide. European Urology Oncology. 2018;1:238-41.
    13. Rachner TD, Tsourdi E, Hofbauer LC. Apalutamide and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018;378:2541-2.
    14. Smith MR, Yu MK, Small EJ. Apalutamide and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018;378:2542.
    15. Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, et al. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018.
    16. Attard G, Saad F, Tombal B, Hussain M, Sternberg CN, Phung D, et al. Health-related quality of life (HRQoL) deterioration and pain progression in men with non-metastatic castration-resistant prostate cancer (M0 CRPC): Results from the PROSPER study. J Clin Oncol. 2018;36:abstr 5010.
    Published April 16, 2019
  • Using prognosis to guide early detection and treatment selection in non-metastatic prostate cancer.

    Over recent years there has been an increasing awareness that our ideas on the lethality of primary non-metastatic prostate cancer may need to change. This concept has emerged from a number of different sources including randomised controlled trials, reports from mature active surveillance programmes and prognostic modelling work in large populations (1-2).

    Published December 5, 2018
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